Treatment of Low Bone Density in Cystic Fibrosis.

Cystic Fibrosis Clinical Trial

— OSCYF  

Official title:

Osteoporosis in Cystic Fibrosis: Study of Bone Mass and Bone Metabolism, and Prospective Randomized Therapeutic Trial.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01812551
• Other study ID #: 02A001
• Status: Completed
• Phase: Phase 3
• First received: March 14, 2013
• Last updated: March 5, 2014
• Start date: October 2002
• Est. completion date: July 2007

Study information

• Verified date: March 2014
• Source: Istituto Auxologico Italiano
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

Cystic fibrosis (CF) -- an autosomal recessive genetic disease affecting about 60,000 individuals worldwide, including about 3,800 in Italy -- is often associated with low bone mineral mass. The current aggressive therapies have ensured a much longer survival of CF patients but this has led to a higher frequency of osteoporosis and bone fractures, a serious problem which not only affects quality of life, but also hinders further therapeutic measures.

The aim of this study, conducted on a large group of children, adolescents and young adults with CF, has been the evaluation of bone mass changes after 1 year of a simple treatment with RDA-adjusted dietary calcium plus 25-OH vitamin D supplementation, and the feasibility and efficacy of alendronate treatment (for another year) in patients not responding to calcium + 25-OH vitamin D alone.

Description:

The study included 2 phases.

Phase 1 (1-year open-label observational study): following baseline evaluation, bone mass changes have been studied with a simple therapy of adequate calcium intake and 25-OH vitamin D supplements in all eligible subjects (N=171).

Phase 2 (1-year double-blind, randomized, placebo-controlled, parallel group study): the 128 subjects showing an insufficient response to calcium + 25-OH vitamin D alone (bone mass increase <5%) at the end of Phase 1, were randomized into 2 groups and assigned to alendronate treatment (N=65) or placebo (N=63) (in addition to calcium and 25-OH vitamin D as during Phase 1).

The study has been carried out by the Coordinator's Institution (Istituto Auxologico Italiano)in collaboration with most Regional Reference Centers for CF in Italy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 171
• Est. completion date: July 2007
• Est. primary completion date: July 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 5 Years to 30 Years

Eligibility

Inclusion Criteria:

• age 2-30 years

• clinically stable condition

• regular menses in females

• low Bone Mineral Apparent Density for age (defined as BMAD Z-score =-2.0 if age =18 years or =-2.5 if age >18 years).

Exclusion Criteria:

• two or more episodes of hypercalcemia and/or hypercalciuria

• contraindications to 25-OH vitamin D or alendronate treatment

• recent transplantation

• other diseases or medications (glucocorticoids excepted) associated with bone loss.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis
• Osteoporosis

Intervention

Drug:
• Alendronate
As active drug, we used Alendros (Abiogen Pharma, Pisa, Italy), distributed to the patients in plain bottles and boxes (bearing only the center and patient codes).
• Placebo
Placebo was distributed to the patients in plain bottles and boxes (bearing only the center and patient codes).

Locations

Country	Name	City	State
Holy See (Vatican City State)	CRR Fibrosi Cistica, Divisione Gastroenterologia, Ospedale Bambin Gesù	Città del Vaticano
Italy	CRR Fibrosi Cistica, Unità Operativa di Pediatria, Ospedale Misericordia	Grosseto
Italy	CRR Fibrosi Cistica, Clinica Pediatrica, Policlinico Universitario di Messina	Messina
Italy	Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università degli Studi di Milano	Milano
Italy	Istituto Auxologico Italiano IRCCS	Milano
Italy	CRR Fibrosi Cistica, Dipartimento Pediatria, Università Federico II	Napoli
Italy	CRR Fibrosi Cistica Adulti, Azienda Ospedaliera Universitaria San Luigi Gonzaga	Orbassano
Italy	CRR Fibrosi Cistica, Ospedale dei Bambini, ARNAS Civico	Palermo
Italy	CRR Fibrosi Cistica, Dipartimento di Pediatria, Policlinico Umberto I	Roma
Italy	CRR Fibrosi Cistica, Divisione di Pediatria, Istituto Burlo Garofolo	Trieste
Italy	CRR Fibrosi Cistica, Azienda Ospedalierouniversitaria di Verona	Verona

Sponsors (2)

Lead Sponsor	Collaborator
Istituto Auxologico Italiano	Fondazione Telethon

Countries where clinical trial is conducted

Holy See (Vatican City State),  Italy, 

References & Publications (11)

Aris RM, Renner JB, Winders AD, Buell HE, Riggs DB, Lester GE, Ontjes DA. Increased rate of fractures and severe kyphosis: sequelae of living into adulthood with cystic fibrosis. Ann Intern Med. 1998 Feb 1;128(3):186-93. — View Citation

Baroncelli GI, De Luca F, Magazzú G, Arrigo T, Sferlazzas C, Catena C, Bertelloni S, Saggese G. Bone demineralization in cystic fibrosis: evidence of imbalance between bone formation and degradation. Pediatr Res. 1997 Mar;41(3):397-403. — View Citation

Bhudhikanok GS, Lim J, Marcus R, Harkins A, Moss RB, Bachrach LK. Correlates of osteopenia in patients with cystic fibrosis. Pediatrics. 1996 Jan;97(1):103-11. — View Citation

Bhudhikanok GS, Wang MC, Marcus R, Harkins A, Moss RB, Bachrach LK. Bone acquisition and loss in children and adults with cystic fibrosis: a longitudinal study. J Pediatr. 1998 Jul;133(1):18-27. — View Citation

Bianchi ML, Cimaz R, Bardare M, Zulian F, Lepore L, Boncompagni A, Galbiati E, Corona F, Luisetto G, Giuntini D, Picco P, Brandi ML, Falcini F. Efficacy and safety of alendronate for the treatment of osteoporosis in diffuse connective tissue diseases in children: a prospective multicenter study. Arthritis Rheum. 2000 Sep;43(9):1960-6. — View Citation

Brumsen C, Hamdy NA, Papapoulos SE. Long-term effects of bisphosphonates on the growing skeleton. Studies of young patients with severe osteoporosis. Medicine (Baltimore). 1997 Jul;76(4):266-83. Review. — View Citation

Glorieux FH, Bishop NJ, Plotkin H, Chabot G, Lanoue G, Travers R. Cyclic administration of pamidronate in children with severe osteogenesis imperfecta. N Engl J Med. 1998 Oct 1;339(14):947-52. — View Citation

Grey AB, Ames RW, Matthews RD, Reid IR. Bone mineral density and body composition in adult patients with cystic fibrosis. Thorax. 1993 Jun;48(6):589-93. — View Citation

Henderson RC, Madsen CD. Bone density in children and adolescents with cystic fibrosis. J Pediatr. 1996 Jan;128(1):28-34. — View Citation

Henderson RC, Madsen CD. Bone mineral content and body composition in children and young adults with cystic fibrosis. Pediatr Pulmonol. 1999 Feb;27(2):80-4. — View Citation

Humphries IR, Allen JR, Waters DL, Howman-Giles R, Gaskin KJ. Volumetric bone mineral density in children with cystic fibrosis. Appl Radiat Isot. 1998 May-Jun;49(5-6):593-5. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bone mineral density increase at lumbar spine.	Bone mineral density evaluated by DXA. Bone mineral apparent density calculated to correct for bone size (growing subjects). Z-score calculated.; Measurements: Phase 1 (171 subjects): Baseline, 6 months, 12 months. Phase 2 (128 subjects, randomized to 2 arms: placebo or alendronate): 18 months, 24 months.	up to 24 months	No
Secondary	Changes in bone turnover markers.	Bone turnover markers: (serum) osteocalcin (OC), bone specific alkaline phosphatase (BSAP), C-terminal telopeptide of procollagen 1 (CTx); (urine) terminal telopeptide of procollagen 1 (NTx).	baseline and up to 24 months	No
Secondary	Fracture rate.	Appendicular fractures were evaluated at baseline (previous fractures) and throughout the 2 years of study (incident fractures) with X-rays.; Vertebral fractures were evaluated at the end of Phase 1 (12th month) and at the end of Phase 2 (24th month) with lateral thoracic and lumbar spine X-rays.	at 12th and 24th month	No
Secondary	Adverse effects of alendronate.	Evaluated on the basis of lab tests (calcemia, calciuria, blood cell count, liver and kidney function), FEV1 changes, and other signs/symptoms (e.g. pain, fever, etc.)	continuously throughout Phase 2 (2nd year of study)	Yes

External Links

•   Lab test information
•   Study protocol